Planimetry involves direct measurement of MVA by tracing the smallest anatomical orifice area using 2-D or 3-D imaging. MVA by 2-D planimetry is performed in the parasternal short axis view in mid diastole; the measurement plane should be perpendicular to the mitral orifice. Scanning from base to apex of the LV helps identify the true leaflet tips. In DMS and MAC, the calcification of the base and mid-portion of the MV leaflets can cause significant acoustic shadowing which subsequently result in thinner appreciation of leaflets and thus under-estimation of the MVA [16]. Increased echocardiographic gain settings can further exacerbate acoustic shadowing [17].

Pressure half-time (PHT) is the time interval required for the trans-mitral pressure gradient (TMPG) to reduce to half the peak value during diastole. PHT has an inverse relationship with MVA and it is a well-established method for determining MVA in the setting of RMS [18]. PHT of 220 ms has been shown to be equal to MVA = 1 cm${}^2$ by the Gorlin equation. Estimation of MVA by utilization of PHT is affected by the compliance of left atrium and LV, and estimated MVA can be increased or decreased based on left atrium and LV compliance [17, 18]. Among patients with DMS who frequently multiple comorbidities have such as diabetes mellitus, CKD, and cardiovascular disease, PHT cannot accurately estimate MVA [19, 20, 21]. Similarly, among DMS patients, left atrial compliance can also vary from normal in these patients (increased LV filling pressure, tachycardia, atrial fibrillation), thus PHT is not routinely recommended in patients with DMS [17].

The proximal iso-velocity surface area (PISA) method is based on the concepts of fluid convergence and conservation of mass. As a fluid stream converges towards a narrow orifice, flow accelerates and forms multiple hemispheric shells of increasing velocity and decreasing radius. In order for the mass to be conserved, flow at any of these hemispheric shells must equal flow across the orifice. Incorporating the radius of the convergence hemisphere, aliasing velocity, peak mitral inflow velocity and the opening leaflet angle relative to the flow direction, MVA can be calculated. The iso-velocity shell changes throughout the systole so measuring the largest shell, using frame by frame analysis, can be erroneous. Multiple independent manual measurements can introduce significant errors, even when performed by experienced users [22]. In the setting of coexisting mitral regurgitation, color Doppler assessment of the hemispheric convergence of the mitral diastolic flow on the atrial side of the MV can be technically challenging and requires a high level of expertise. The effect of variable heart rate, such as seen in atrial fibrillation (present in 30% of DMS patients) can further limit its accuracy [17, 23].

The continuity equation is an extrapolation of the concept of conservation of mass, and states that in the absence of valvular regurgitation or intracardiac shunting, the trans-mitral stroke volume (SV) should be equal to the SV determined at the level of the left ventricular outflow tract (LVOT) or right ventricular outflow tract (RVOT) [21]. As SV = valve area x velocity time integral (VTI), one can deduce that MVA = LVOT SV/VTI-MV (in the absence of significant mitral or aortic regurgitation). Calcium may extend into the aorto-mitral curtain affecting calculation of the LVOT cross-sectional area; another source of error when using the continuity equation method is the assumption of a circular shape for the LVOT [24]. To overcome these issues, a dimensionless mitral stenosis index (DMSI) = (LVOT-VTI/MV-VTI) has been proposed (Fig. 1A, [25]). A DMSI of 0.35 to 0.50 is consistent with severe DMS (MVA $\le$1.5 cm${}^2$), and a DMSI 0.35 suggests very severe calcific MS (MVA $\le$1.0 cm${}^2$). A nonsignificant trend toward increased risk mortality was observed with MVACEQ $\le$1.0 cm${}^2$ and DMSI $\le$0.35 with 50% mortality in the DMS cohort at 1 year (Fig. 1B) [25]. However, this tool cannot be used in patients with significant left sided regurgitation as VTI across aortic or mitral valve would be higher and this may over or overestimate stenosis severity.

Fig. 1.

Dimensionless Mitral Stenosis Index. (A) Calculation of dimensionless mitral stenosis index (DMSI) which is derived by dividing left ventricle outflow tract (LVOT) velocity time integral (VTI) by MV VTI. (B) Nonsignificant trend toward increased risk of mortality was observed with MVACEQ $\le$1.0 cm${}^2$ and DMSI $\le$0.35 with 50% mortality in the DMS cohort at 1 year [25].

Peak and mean trans-mitral gradients are important parameters to assess in DMS. Peak TMG, measured by Continuous Wave Doppler (CW) across the MV using the simplified Bernoulli equation (4 $\times$ v${}^2$), is highly variable and influenced by left atrial compliance and LV diastolic dysfunction [26]. Mean TMG is obtained by tracing the CW envelope of mitral inflow and is more reflective of valvular stenosis. Pulsed wave Doppler at MV leaflet tips is used to measure the early (E) and late (A) diastolic velocities [17]. In one study of patients with severe MAC and a MVA $\le$1.5 cm${}^2$, E velocity was significantly elevated compared to those with MVA $>$1.5 cm${}^2$ with no difference in A velocity or E to A ratio between the 2 groups [27].

In patients with RMS, Doppler-derived mean TMG values correlate well with invasive measurements obtained via trans-septal catheterization [28]. Such validation studies are lacking for DMS patients. There is a poor correlation seen between mean gradients and MVA using the continuity equation in DMS [25]. This lack of correlation can be attributed to different issues with trans-mitral flow, increased heart date (i.e., shortened diastole), and decreased left atrial and LV compliance in patients with diastolic dysfunction [17]. Given that the pressure gradient is directly related to the squared function of transvalvular flow rate [29], high cardiac output states in patients with advanced CKD or end-stage renal disease (ESRD) — which are seen in almost 19% of patients with DMS [23], may increase trans-mitral gradients in the absence of significant stenosis [30, 31]. On the other hand, lack of contraction of flow due to tunnel-like morphology as well as low flow state seen in elderly women may lower the trans-mitral gradient in MV and underestimate DMS severity. TMPG $\ge$8 mmHg in severe DMS (MVA by continuity equation 1.5 cm${}^2$) was independently associated with 1-year mortality in a study of 200 patients in those with MVA by 1.5 cm${}^2$ by CEQ, while another study of 5754 patients with mean MV gradient $\ge$3 mmHg also found an association between MV gradient and mortality (adjusted HR 1.064 per 1 mmHg increase 95% CI 1.049–1.080) [32].

Although transthoracic echocardiography (TTE) can provide a good estimation of the burden of MAC, in severe MAC, the calcification can create an echocardiographic artifact and creates acoustic shadowing but lacks the echo-lucent center which might obscure the valve assessment and [33]. Transesophageal echocardiography (TEE) can provide better visualization of the mitral annulus and left ventricle thickness and can accurately assess the extension of MAC to the surrounding structure [33, 34]. TEE has the superiority of temporal resolution over TTE, and thus it is the method of choice to further evaluate and characterize the MV function, extent of calcification, and the leaflet characterization [35]. Cardiac computed tomography scan on the other hand as higher isotopic spatial resolution with excellent calcification definition [36].

Three-dimensional echocardiography provides multiplanar reconstruction of valvular anatomy and the extension of MAC. However, the presence of high burden calcification might create acoustic shadowing which subsequently hinders the complete analysis of the sub-valvular apparatus or left ventricular outflow tract [35]. To minimize this false measurement, a zoomed view at the tip of the mitral leaflet and using planimetry method to trace the MV orifice when the valve is wide open in the diastolic frame [37]. The other advantages of 3D over 2D include the ability to rotate the images and examine the MV from different perspectives and formulate a relationship between the MV and its surrounding structures [37, 38].

It is imperative to evaluate tricuspid valve and pulmonary artery systolic pressure (PASP) as part of the markers of progression of MV disease. In the absence of an alternative explanation of elevated PASP in the setting of MV stenosis, this elevation of PASP could have hemodynamic consequences on the progression of MV stenosis. It is not uncommon to have normal resting PASP even in the presence of severe MV stenosis; however, as the disease progresses, more dilated right ventricle and worsening in the tricuspid regurgitation of tricuspid leaflet tethering could occur [37, 39]. Furthermore, the marked disparity between the valve area between MS and the tricuspid valve being dilated create the paradoxical (leftward) motion of the septum in the diastole given the early diastolic filling across the tricuspid valve [40]. Severe tricuspid regurgitation can reduce right sided cardiac output leading to low-flow, low-gradient pattern makes the accurate assessment of stenosis more difficult [41].

Kato et al. [23] showed significant improvement in MVA by CEQ (2.00 $\pm$ 0.50 vs. 2.26 $\pm$ 0.62 cm${}^2$p 0.001) in 190 patients with MS (mean gradient $>$4 mmHg) undergoing aortic valve replacement (AVR) and with a significant decrease in gradient post TAVR (5.2 $\pm$ 1.5 vs. 4.7 $\pm$ 1.9 mmHg). This is likely partly related to the improvement in LVOT stroke volume but undermines the issue of flow dependency of transmitral gradients and MVA CEQ. However, in patient with true MS, MVA remained 2.0 cm${}^2$ after AVR, mean TMG and LVOT SV did not change significantly after AVR. In patients with true MS, extension of calcification of the leaflets was more frequently observed and LVOT SV and AVA was smaller than those with pseudo severe stenosis. MVA $\le$1.5 cm${}^2$ CEQ and mitral annular distension $\le$1 mm or extension of calcification to both anterior and posterior mitral leaflets suggested the presence of true mitral stenosis. No clear validated diagnostic tool is available to differentiate severe from pseudo severe MS, as those with severe MS have higher mortality post AVR AT 2.9 years and will need treatment for both valves simultaneously or sequentially [42].

Diagnosing significant DMS is crucial as worst outcomes have been reported in patient with severe mitral stenosis undergoing TAVR (higher in-hospital mortality and heart failure-related hospitalization at 1-year in severe MS compared to those without MS [43]) and four-fold increase in cardiovascular death, and a 3.9-fold increase in disabling stroke at 30-days in those with MS [44]. In a study 61 serial echocardiograms in 8 patients with severe DMS undergoing TAVR, persistent elevation of mean TMG (6.7 $\pm$ 3 mmHg pr vs. 8.3 $\pm$ 1.5 mmHg Post TAVR) and PASP (52 $\pm$ 22 vs. 32 $\pm$ 8 mmHg, p = 0.048) was seen at 2 years when compared to age and sex-matched controls without DMS potentially explaining the increased mortality seen in this group of patients [42].